Antineuronal Antibodies Against Neurotransmitter Receptors and Synaptic Proteins in Schizophrenia: Current Knowledge and Clinical Implications

When Eugen Bleuler coined the term ‘schizophrenia’ he believed that various causes of illness may underlie this disease. Currently, neurodevelopmental abnormalities and consecutive impairments in dopaminergic and glutamatergic neurotransmission are considered as major causes of schizophrenia. However, there are various indications for involvement of immune processes, at least in subgroups of patients. Circulating antineuronal antibodies provide a promising link between the well-described disturbances in neurotransmission and the immune hypothesis of schizophrenia. This review summarizes important studies that have examined the role of glutamate, dopamine, acetylcholine and serotonin receptor autoantibodies, and other antineuronal antibodies against synaptic proteins in the serum of patients diagnosed with schizophrenia. Currently, it is not known whether the presence of antineuronal antibodies in blood should be considered as a causal or disease-modulating factor in schizophrenia. Due to emerging evidence regarding the important role of the blood–brain barrier, combined testing of serum and cerebrospinal fluid is likely to be more appropriate to answer this question than pure serum analyses. We suggest implementation of such testing in first-onset and treatment-resistant patients as part of the diagnostic process. In addition, future clinical trials should evaluate if immunotherapy (e.g. cortisone pulse therapy, intravenous immunoglobulins, plasmapheresis, rituximab, or cyclophosphamide) is helpful in cases with a neuroinflammatory component.